Osteoprotegerin is associated with depletion of circulating endothelial progenitor cells and elevation in pulmonary arterial pressure in patients with systolic heart failure

Abstract

Objective Osteoprotegerin (OPG) may predict progression of chronic congestive heart failure (CHF) with increased mortality and play an important role in the development of pulmonary arterial hypertension (PAH). Mounting evidence suggests that PAH developed during CHF is not solely caused by a “passive” increase from the left ventricular end-diastolic pressure, but rather a “reactive” response from contributing lung endothelial dysfunction and vascular remodelling, a pathological process that can be signifi cantly infl uenced by endothelial progenitor cells (EPCs). This study aims to examine whether circulating EPCs from patients with CHF are aff ected and if OPG could be implicated during disease progression.

Methods In this study EPCs were isolated, cultured, and quantifi ed from patients of CHF with (n = 20) or without PAH (n = 40) as measured by right heart catheterization. Serum levels of OPG and N-terminal pro-brain natriuretic peptide (NT- pro BNP) were analysed and correlated with EPCs.

Results A signifi cant decrease in circulating EPCs (39.3 ± 9.1 vs 67.1 ± 10.5 EPCs/×200 fi eld; P < 0.05) was found in CHF patients who developed PAH compared to those without PAH. Both OPG (551.90 ± 49.83 vs 312.29 ± 31.12 pg/ml; P < 0.05) and NT-pro BNP (2,946.50 ± 1,434.50 vs 1,328.20 ± 811.90; P < 0.05) were also signifi cantly elevated in CHF patients with PAH. Circulating level of OPG correlated inversely with EPCs (r=–0.45, P= 0.037) but positively with mPAP (r = 0.53, P= 0.011).

Conclusions Our study demonstrates that OPG elevation and EPC depletion are associated with CHF patients who have developed PAH. The inverse relationship of circulating OPG with EPCs suggests a possible mechanism for OPG in the development of pulmonary vascular dysfunction, thus worsening prognosis for CHF patients.

Key Words:

• Osteoprotegerin
• congestive heart failure
• pulmonary arterial hypertension
• endothelial progenitor cells.